IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.

Inflammation Clinical Trial

— IMPACT  

Official title:

Instant MSC Product Accompanying Autologous Chondron Transplantation (IMPACT): Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02037204
• Other study ID #: IMPACT
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2013
• Est. completion date: April 2016

Study information

• Verified date: June 2018
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Articular cartilage defects in the knee have a poor intrinsic healing capacity and may lead to functional disability and osteoarthritis. Cartilage cell therapy using autologous chondrocyte implantation (ACI) has been established as the first advanced treatment therapy medicinal product. Although this technique has achieved good mid-term results, it is a costly and extensive two-stage procedure which is limited by the number of chondrocytes obtained by biopsy and the dedifferentiation resulting from the expansion phase. Therefore, there is a need for improvement. A new cartilage repair technique should aim at decreasing surgical trauma, lowering complexity, improving logistics and cost-effectiveness while retaining or improving clinical outcome. Direct contact between mesenchymal stromal cells (MSCs) and dedifferentiated articular chondrocytes in vitro showed improvement of the chondrogenic phenotype of dedifferentiated articular chondrocytes. In addition, preserving the pericellular matrix of chondrocytes improves cartilage formation. These chondrons (chondrocytes with their pericellular matrix) have shown improved cartilage formation when combined with allogeneic MSCs in extensive preclinical studies. The cells are mixed with fibrin cell carrier and applied to the cartilage lesion within one surgical procedure. This will reduce patient morbidity and improve patient care through immediate transplantation of a potent cell-based cartilage product. This is a phase I/II prospective monocenter study to evaluate the safety and feasibility of the IMPACT for treatment of focal articular cartilage lesions of the knee.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Age >18 and <45 years old

• Symptomatic isolated full-thickness articular cartilage lesion on the femoral condyle or trochlea.

• Size 2 - 8 cm2

• Intact anterior cruciate ligament

Exclusion Criteria:

• (History of) osteoarthritis, defined as Kellgren-Lawrence grade >3 as determined from appropriate X-ray.

• Concomitant inflammatory disease that affects the joint (rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis)

• (History of) Septic arthritis.

• Malalignment requiring an osteotomy.

• (History of) total menisectomy in the target knee joint.

• Any surgery in the knee joint 6 months prior to study inclusion.

• Risk groups for MRI scanning due to the magnetic field like patients with pacemakers, nerve stimulators, metal particles, stents, clips or implants, (possible) pregnancy or breast feeding.

• Patients with severe anxiety for MRI scans and/or needles

Related Conditions & MeSH terms

• Effusion (L) Knee
• Foreign Bodies
• Foreign-Body Reaction
• Inflammation
• Knee Pain Swelling

Intervention

Other:
• Cartilage repair surgery
Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs

Locations

Country	Name	City	State
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
UMC Utrecht

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

Bekkers JE, Creemers LB, Tsuchida AI, van Rijen MH, Custers RJ, Dhert WJ, Saris DB. One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats. Osteoarthritis Cartilage. 2013 Jul;21(7):950-6. doi: 10.1016/j.joca.2013.03.015. Epub 2013 Apr 9. — View Citation

Bekkers JE, Tsuchida AI, van Rijen MH, Vonk LA, Dhert WJ, Creemers LB, Saris DB. Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. Am J Sports Med. 2013 Sep;41(9):2158-66. doi: 10.1177/0363546513494181. Epub 2013 Jul 5. — View Citation

Vonk LA, Doulabi BZ, Huang C, Helder MN, Everts V, Bank RA. Preservation of the chondrocyte's pericellular matrix improves cell-induced cartilage formation. J Cell Biochem. 2010 May;110(1):260-71. doi: 10.1002/jcb.22533. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Structural Repair	To examine parameters of structural repair at one year after treatment using MRI and a second-look arthroscopy.	12 months
Other	Health Care Use and Costs	To assess the healthcare use and costs related to the procedure as well as the health-related work leave during the study period.	18 months
Primary	Safety: Adverse Events	Adverse events rate	18 months
Secondary	Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score	Clinical improvement as measured by patient reported outcome scores. The questionnaire has been developed to evaluate the symptoms and limitations for patients with osteoarthritis. The outcome of the KOOS-scale varies from 0-100, where 0 indicates the greatest possible problems and is the worst outcome and 100 indicates no problems.	3 and 18 months

External Links

•   IMPACT animation
•   Trials Register of the European Union